EP2674478A1 - Kulturvorrichtung - Google Patents

Kulturvorrichtung Download PDF

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Publication number
EP2674478A1
EP2674478A1 EP13170979.2A EP13170979A EP2674478A1 EP 2674478 A1 EP2674478 A1 EP 2674478A1 EP 13170979 A EP13170979 A EP 13170979A EP 2674478 A1 EP2674478 A1 EP 2674478A1
Authority
EP
European Patent Office
Prior art keywords
culture
unit
cell
connecting portions
culture device
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP13170979.2A
Other languages
English (en)
French (fr)
Inventor
Sheng-nan CHANG
Sheng-Chih Chang
Chyung Ay
Cheng-Nan Chen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP2674478A1 publication Critical patent/EP2674478A1/de
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/26—Constructional details, e.g. recesses, hinges flexible
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/46—Means for fastening
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/02—Membranes; Filters

Definitions

  • This invention relates to a culture device, more particularly to a culture device adapted to engage a stretching device.
  • cells of the subject are usually in a dynamic state and are subjected to force stimulation.
  • force stimulation resulting from, e.g., body movement (such as walking, running, etc.), blood-vessel pulsation, respiration,peristalsis,andfiltrationin urinarysystem would cause deformation of cells.
  • the force stimulation not only influences morphology of the cells but also affects cell proliferation, cell differentiation, apoptosis, cell migration, remodeling of extracellular matrix and gene expression.
  • U.S. Patent No. 4789601 discloses a cell culture apparatus 1 including a plurality of wells 11, each of which contains an elastomeric membrane 12 for culturing cells thereon.
  • a rubber gasket 13 formed with a plurality of apertures 131 is superposed on a plenum 14 formed with a plurality of vacuum channels 141.
  • the vacuum channels 141 are in fluid communication with the apertures 131.
  • the cell culture apparatus 1 is superposed on the rubber gasket 13, and vacuum equipment is used to pull the elastomeric membrane 12 downwardly by extracting air from the vacuum channels 141. When the air extraction is stopped, the elastomeric membranes 12 return to the original position shown in Figure 1 .
  • the deformation of the elastomeric membrane 12 would provide physical stimulation to the cells cultured on the elastomeric membrane 12.
  • the aforementioned equipment and operating method can provide physical stimulation for the cells, due to elastic fatigue, the elastomeric membranes 12 are likely to be permanently distorted even without air extraction. Therefore, the force stimulation and the subsequent observation of cell morphology are adversely influenced. Furthermore, the vacuum equipment would make loud noise and the deformation degree would be undesirably changed due to the compressible property of the gas.
  • European Patent Application Publication No. 1734110 A1 discloses a culture device 2 having elastic and deformable properties.
  • the culture device 2 includes a bottom membrane 21 and side walls 22 upstanding from the entire periphery of the bottom membrane 21.
  • the bottom membrane 21 and the side walls 22 cooperatively define a space 23 for culturing cells 200 (see Fig. 4 ).
  • Engagement holes 221 are formed in opposing side walls 22 on a line extended from a periphery edge of the bottom membrane 21.
  • a stretching device 3 is used to engage the culture device 2 to provide stretching force to the culture device 2.
  • the stretching device 3 includes a rail plate 31, a fixed plate 32 which is fixed to the rail plate 31, a movable plate 33 which is disposed slidably on the rail plate 31, and pins 321, 331 protruding from the fixed plate 32 and the movable plate 33, respectively.
  • the pins 321, 331 are inserted into the engagement holes 221 of the culture device 2.
  • a step motor 35 controlled by a control device 34 is used to move the movable plate 33 away from the fixed plate 32.
  • the aforesaid culture device 2 can solve the problems encountered in U.S. Patent No. 4789601 , the force transmitted to the side walls 22 from the pins 331 would be gradually decreased from the pins 331. Therefore, the bottom membrane 21 may be pulled and deformed unevenly.
  • the side walls 22 have the properties of elasticity and deformability that are liable to result in permanent distortion of the engagement holes 221 after long term use, thereby resulting in more uneven stretching force.
  • the side walls 22 may not be hard enough to stand against the stretching force. If the hardness of the culture device 2 is raised entirely, the bottom membrane 21 may be too hard to be deformed.
  • the object of the present invention is to provide a culture device that can overcome the aforesaid drawbacks of the prior art.
  • a culture device adapted to engage a stretching device, which includes a deformable cell-culture unit that includes a culture membrane and a surrounding wall extending upwardly from a periphery of the culture membrane, and a deformable engaging unit that is connected to the surrounding wall of the deformable cell-culture unit.
  • the engaging unit is adapted to engage the stretching device, and that has a hardness larger than that of the cell-culture unit.
  • the first preferred embodiment of a culture device 4 of the present invention includes a deformable cell-culture unit 5 and a deformable engaging unit 6.
  • the engaging unit 6 is connected to the cell-culture unit 5 and has a hardness larger than that of the cell-culture unit 5.
  • the cell-culture unit 5 is stretchable and the hardness thereof ranges between 10 Shore A and 59 Shore A.
  • the engaging unit 6 is stretchable and the hardness thereof ranges between 60 Shore A and 90 Shore A.
  • the hardness of the cell-culture unit 5 is 30 Shore A
  • the hardness of the engaging unit 6 is 70 Shore A.
  • the cell-culture unit 5 includes a rectangular culture membrane 51 and a surrounding wall 52 which extends upwardly from a periphery of the culture membrane 51.
  • the surrounding wall 52 is also in a shape of a rectangle and has two opposite first side walls 521 and two opposite second side walls 522 interconnecting the first side walls 521.
  • the engaging unit 6 is connected to the surrounding wall 52 of the cell-culture unit 5.
  • the engaging unit 6 includes two connecting portions 61 connected to the second side walls 522 of the surrounding wall 52, respectively.
  • Each of the connecting portions 61 has upper and lower surfaces and is formed with opposite upper and lower grooves 612, 613 that are indented inwardly from the upper and lower surfaces, respectively.
  • Each of the connecting portions 61 further has opposing end surfaces 614 that interconnect the upper and lower surfaces and that are, in this embodiment, flush with the first side walls 521, respectively.
  • the upper and lower grooves 612, 613 of each of the connecting portions 61 extend along a longitudinal direction (D1) of the second side walls 522 of the surrounding wall 52 and terminate at the end surfaces 614.
  • Each of the connecting portions 61 includes a body segment 611, two upper tooth segments 616 extending upwardly from the body segment 611 and cooperatively defining the upper groove 612 with the body segment 611, and two lower tooth segments 617 extending downwardly from the body segment 611 and cooperatively defining the lower groove 613 with the body segment 611.
  • Each of the second side walls 522 of the surrounding wall 52 in Figure 5 has an indent 523.
  • Each of the connecting portions 61 further includes a protrusion 618 extending from the body segment 611 in a lateral direction (D2) perpendicular to the longitudinal direction (D1) and engaging the indent 523 of a respective one of the second side walls 522.
  • the indent 523 can be formed in each of the connecting portions 61, and the protrusion 618 can be formed on each of the second side walls 522.
  • the indent-protrusion structure would increase contact surface area, thereby improving connecting force between the protrusion 618 and the indent 523 and prolonging service life.
  • Each of the cell-culture unit 5 and the engaging unit 6 can be made from, e.g., silicone, polydimethylsiloxane (PDMS), ⁇ -caprolactone (PCL), or poly(latide-co-glycolide acid) (PLGA).
  • the cell-culture unit 5 and the engaging unit 6 are made from silicone.
  • the hardness of the cell-culture unit 5 and the engaging unit 6 can be controlled by process conditions or addition of a curing agent.
  • the culture membrane 51 is preferably transparent and has a thickness suitable for observation under a microscope, e.g., 0.2 mm.
  • the protrusion 618 and the indent 523 align and engage with each other, followed by a thermocompression bonding so as to form the culture device 4 (see Figure 6 ).
  • the culture device 4 can be made by injection molding.
  • the shape of the culture device 4 is not limited to the rectangular shape of this embodiment and can be other shapes suitable for this invention.
  • Figure 7 shows use of the culture device 4 with a stretching device 7.
  • the stretching device 7 includes a clamping unit 71.
  • the clamping unit 71 has a length in the longitudinal direction (D1), that is substantially the same as that of the upper and lower grooves 612, 613 of each of the connecting portions 61.
  • the clamping unit 71 is retained in the upper and lower grooves 612, 613 of each of the connecting portions 61, and the stretching device 7 provides a force to the culture device 4 so that the cell-culture unit 5 and the connecting portions 61 are stretched so as to provide physical stimulation to the cells.
  • one of the connecting portions 61 can be fixed and the other one of the connecting portions 61 is pulled by the stretching device 7 so that the culture membrane 51 is stretched in the lateral direction (D2). Since the structure and the operation of the stretching device 7 are not the features of this invention, detailed descriptions thereof are omitted herein for the sake of brevity.
  • the shape of the grooves should not be limited in this preferred embodiment, and can be modified based on the configuration of the clamping unit 71 of the stretching device 7.
  • the upper and lower grooves 612, 613 of each of the connecting portions 61 are tapered inwardly from the upper and lower surfaces of each of the connecting portions 61, respectively.
  • the upper groove 612 of each of the connecting portions 61 has a width in the lateral direction (D2). The width is increased from the body segment 611 to a tip of each of the upper tooth segments 616.
  • a width of the lower groove 613 of each of the connecting portions 61 in the lateral direction (D2) is increased from the body segment 611 to a tip of each of the lower tooth segments 617.
  • Figures 9 and 10 show the second preferred embodiment of the culture device 4 of the present invention.
  • the second preferred embodiment is similar to the first preferred embodiment except that, in this embodiment, the cell-culture unit 5 further includes two partition walls 53 each of which interconnects the second side walls 522 of the surrounding wall 52 so as to divide the culture membrane 51 into three spaced-apart culturing regions 511.
  • the number of the partition walls 53 could vary depending on actual requirements.
  • the cells can be cultured and assessed in different experimental conditions under an identical stretching environment, thereby improving experimental convenience.
  • the partition walls 53 are designed to extend in the lateral direction (D2) which is parallel to a stretching direction, the force applied to each of the culturing regions 511 would be substantially identical.
  • the engaging units 6 can endure greater stretching force and provide desirable hardness and elasticity to the culture device 4. Moreover, since the upper and lower grooves 612, 613 are designed to extend along the longitudinal direction (D1) and to terminate at the end surfaces 614, when the same engage the aforesaid clamping unit 71, a relatively even stretching force can be applied to the culture device 4.
EP13170979.2A 2012-06-13 2013-06-07 Kulturvorrichtung Withdrawn EP2674478A1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
TW101121012A TW201350571A (zh) 2012-06-13 2012-06-13 生物力學測試用之載具

Publications (1)

Publication Number Publication Date
EP2674478A1 true EP2674478A1 (de) 2013-12-18

Family

ID=48578849

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13170979.2A Withdrawn EP2674478A1 (de) 2012-06-13 2013-06-07 Kulturvorrichtung

Country Status (5)

Country Link
US (1) US20130337554A1 (de)
EP (1) EP2674478A1 (de)
JP (1) JP2013255494A (de)
CN (1) CN103484361A (de)
TW (1) TW201350571A (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106867888A (zh) * 2017-03-20 2017-06-20 北京理工大学 可实时在位观测的匀速对称单轴拉伸细胞力学装置
TWI702394B (zh) * 2018-11-16 2020-08-21 京元電子股份有限公司 用於生物晶片測試之彈性緩衝座及其測試模組與測試設備
CN111220767A (zh) * 2018-11-23 2020-06-02 京元电子股份有限公司 用于生物芯片测试的弹性缓冲座及其测试模块与测试设备
US11313851B2 (en) * 2019-02-28 2022-04-26 Nihon Kohden Corporation Device, system, and kit for measuring tension of cell structure containing muscle cells
CN111423983B (zh) * 2020-04-08 2022-03-15 中国科学院力学研究所 一种可扩张基底细胞连续扩增培养器
CN111423980B (zh) * 2020-04-08 2022-03-15 中国科学院力学研究所 一种全密闭细胞基底拉伸和流动剪切复合加载实验系统
EP4324908A1 (de) * 2022-08-17 2024-02-21 International Centre For Genetic Engineering And Biotechnology - ICGEB Endeffektor zur volumetrischen stimulation von zellen

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4789601A (en) 1987-05-04 1988-12-06 Banes Albert J Biocompatible polyorganosiloxane composition for cell culture apparatus
US5217899A (en) * 1990-08-24 1993-06-08 The General Hospital Corporation Cell stretching apparatus
US6472202B1 (en) * 1998-05-08 2002-10-29 Flexcell International Corporation Loading station assembly and method for tissue engineering
EP1428869A1 (de) * 2001-08-30 2004-06-16 Takagi Industrial Co., Ltd. Zell- und strukturinkubator
EP1734110A1 (de) 2004-03-11 2006-12-20 Nagoya Industrial Science Research Institute Kulturvorrichtung

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US4744187A (en) * 1987-01-27 1988-05-17 The Firestone Tire & Rubber Company Mechanical roof fastener
US5686303A (en) * 1994-12-30 1997-11-11 Korman; Joshua Method of growing vertebrate skin in vitro
US6037141A (en) * 1998-06-04 2000-03-14 Banes; Albert J. Culture compression device
WO2005090548A1 (ja) * 2004-03-19 2005-09-29 Nagoya Industrial Science Research Institute 培養器用保持装置
WO2007052653A1 (ja) * 2005-10-31 2007-05-10 Strex Incorporation 培養容器および培養装置
JPWO2007123035A1 (ja) * 2006-04-18 2009-09-03 ストレックス株式会社 培養器
CN201027061Y (zh) * 2007-03-12 2008-02-27 帆宣系统科技股份有限公司 玻璃基板承载具结构
US20120001052A1 (en) * 2010-07-03 2012-01-05 Adil Aliyevich Aliev Apparatus for holding or suspending various articles from an upwardly facing horizontal edge

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4789601A (en) 1987-05-04 1988-12-06 Banes Albert J Biocompatible polyorganosiloxane composition for cell culture apparatus
US5217899A (en) * 1990-08-24 1993-06-08 The General Hospital Corporation Cell stretching apparatus
US6472202B1 (en) * 1998-05-08 2002-10-29 Flexcell International Corporation Loading station assembly and method for tissue engineering
EP1428869A1 (de) * 2001-08-30 2004-06-16 Takagi Industrial Co., Ltd. Zell- und strukturinkubator
EP1734110A1 (de) 2004-03-11 2006-12-20 Nagoya Industrial Science Research Institute Kulturvorrichtung

Also Published As

Publication number Publication date
TWI445821B (de) 2014-07-21
TW201350571A (zh) 2013-12-16
US20130337554A1 (en) 2013-12-19
JP2013255494A (ja) 2013-12-26
CN103484361A (zh) 2014-01-01

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